What DNA Methylation Testing Can Tell You About Your

Health
Analysis by Dr. Joseph Mercola  Fact Checked

STORY AT-A-GLANCE -

 TruDiagnostic is a commercial testing system that determines your biological age, as

opposed to your chronological age, by measuring your DNA methylation

 Your genes have promoter sites at the beginning of the DNA strand, and methylation is
measured at those sites. The level of methylation at the promoter site correlates to the
degree of expression of that particular gene

 Biological aging is a primary cause for chronic disease. If everyone in the world were to
be seven years younger biologically than their chronological age, the global disease
burden would be reduced by 50%

 Patients who contracted COVID-19 were found to have telomere length shortening, but
while people over age 50 showed increased biological aging as a result of the infection,
people younger than 50 had the converse effect, actually getting biologically younger

 Among the more exciting antiaging therapies now available are very small embryonic-like
stem cells (Vsels), which have shown multiyear age reversals even after a single
treatment. Other promising therapies are senolytics and plasma exchange apheresis

Ryan Smith is the founder of TruDiagnostic, a commercial testing system that tests your
biological age, as opposed to your chronological age. It's can be a profoundly useful
tool, because you need an objective barometer to tell you whether or not the things
you're doing to improve your health are actually having the desired impact.
TruDiagnostic was founded in March 2020, right as the COVID pandemic hit, and the
first commercial testing began in July that year. Since then, the company has launched
more than 30 ongoing clinical trials, looking at a variety of interventions. They're also
looking at how COVID-19 affects health metrics and longevity.

"We've built out new algorithms, new ways to read these DNA methylation
markers that we measure for other functional health benefits," Smith says.
"DNA methylation is a really robust platform. But it's also very new. We even
have ways to look at how much arsenic or heavy metals you've been exposed to
over your entire life, how many plastics you've been exposed to.

If there's one thing to take away from this talk, I think it's that this epigenetic
platform will change every area of medicine as a diagnostic, which is
changeable, but also can tell us a lot about different areas of medicine and
really fit a need that we don't have in a lot of diagnostics.

So, I'm very excited about the field, but particularly aging — how to quantify that
process, and then hopefully how to reverse it so that we can have really good
results on increasing people's health span and life span, making them not only
live longer, but live a high-quality life as well."

What Is DNA Methylation?

The idea of epigenetic methylation is rooted in the concept that every cell in your body
has the exact same DNA, but express that DNA in very different ways. The cells of your
skin do not express the same genes as your heart cells, for example.

We now know that the expression of genes is regulated, in part, epigenetically. As your
cells differentiate into different types of tissues, they change their epigenetic expression
to regulate what genes are turned on and turned off.

"I liken it to a light bulb. You can have an engineer look at a light bulb and tell
you exactly what it's made for and how to turn it on, but if you don't know if it's
 on or off, then you're missing a big point of why it was created. It's the same
with our cells.

This idea of measuring how things were turned on or turned off in our DNA
expression has been known for a long time, but only recently scaled to a
platform where we can actually investigate this on a large scale. So, what we
measure is DNA methylation."

DNA methylation is the silencing of gene transcription. Your genes have promoter sites
at the beginning of the DNA strand, and methylation is measured at those sites. The
level of methylation at the promoter site correlates to the degree of expression of that
particular gene.

"The converse process is a process called acetylation, which is a charged

molecule which can open up those proteins to allow your genes to be
transcribed [i.e., the turning on of the gene]. We measure specifically just that
negative regulatory process, the DNA methylation," Smith explains.

What's being measured is not your ability to methylate or not methylate. Rather, it
measures the actual expression of your DNA. And, contrary to conventional genetic
testing like 23andMe, which is done once, DNA methylation can be measured multiple
times as the actual expression of your DNA is alterable and changes over time.

"Due to advances with big data analysis and artificial intelligence, what we're
able to do is take large scales of that data, so we can look at over 900,000
locations in your genome to see what the percentage of methylation is. Then we
can correlate it to several different things."

DNA Methylation and Aging

Biological aging was one of the first things to be looked at using this platform because
there was such a high correlation between DNA methylation and aging. Publications on
this go back to 2009. In 2013, Dr. Steven Horvath created a chronological age-trained
methylation clock, which, with just a couple nanograms of DNA, could help determine
how old, chronologically, an individual was. Ryan states:

"It elucidated this idea that aging, the aging process, can actually be quantified
very, very accurately, but also might even be responsible for a lot of the health
considerations we see with age.

It's important to note that aging is the No. 1 risk factor for all chronic disease
and death. If there's one thing you could do in a lifestyle capacity to prevent the
development of age-related diseases, it is to essentially not age.

So that's a goal, but it's also a very difficult one to measure and do, because
chronological age has been our only measurement for this for some time. We
all know people in their 70s who look like they're in the 50s. We all know people
in their 50s who look like they're in their 70s. So, chronological age has never
been the best measurement. This molecular measurement can give us a much
better idea of how we're aging."

The field of epigenetics is still in its infancy, and there are many fascinating areas of
study underway. For example, there are already products on the market that are able to
help diagnose up to 50 types of cancer from a single blood test.

Researchers are also looking senolytic clocks, which can be useful in the treatment of
COVID, as they can tell you the overall burden of senescence in your body, and whether
you might benefit from senolytic products.

How TruDiagnostic Compares to Other Companies

When asked how TruDiagnostic compares to other companies working with similar
platforms, Smith replies:

"There are three things I like to draw attention to whenever I get asked that
question. The first is the breadth of the measurement. With new clocks and new
analyses coming out every day, one of the important things is making sure that
you're measuring a lot of data, because as these new clocks or new algorithms
come out, you want to be able to update them to make them even more
accurate and more insightful.

So, one of the core tenets of what we wanted to do was to measure a lot of
DNA. We measure over 900,000 locations. That is generally out of 26 million,
approximately. So, it's still a very small amount of the total, but it's significantly
more than any of our competitors, which might be measuring at most a
100,000.

So, we definitely like to scale because this is going to be a forward compatible

platform. The human genome was only recently finished in terms of sequencing
and the same will happen with epigenetic methylation, where, as we learn how
to use this information, we'll be able to interpret it different ways.

We release new reports every three to four weeks with additional insights that
are published in the literature. That way, we can keep everyone informed and up
to date ... We want to provide any of our customers who do our test with the
continuing updates.

Generally, even if someone did a test when we first started, they'll probably be
getting updates for the next decade as we continue to see how this information
and the ability to interpret it progresses ...

The next part of it is the algorithms piece, particularly the interpretation of that
data. We only use published algorithms.

That is one of the things that we are very adamant about because otherwise, if
you don't know how these measurements are related to health outcomes or
related to different therapies, it's like taking the word of a fortune teller ...
Publication is one of the main ways to have that scientifically valid and reliable
measurement.
 [Lastly], the important thing when you're taking these DNA methylation samples
is the tissue that you're taking. We only use blood, the reason being is that most
of these algorithms have been created off of blood samples. One of the
interesting things about epigenetics is that every cell type is different.

If we were to measure your brain with the same algorithm we [used to] measure
your blood, we would get much lower ages than we would on your blood. If we
tested your breast tissue, for instance, we get much higher ages than if we
tested your blood. So, the tissue type is very important, which is why we only
use blood. Although it's not as easy to collect, it is definitely more scientifically
reliable.

So, as you're evaluating which epigenetic companies to use, those would be my

three criteria. Figure out the algorithms that they're using and reporting, make
sure they're published, make sure they're measuring a good number of locations
in case you want to know anything about that sample in the future.

Then lastly, make sure that they're using a collection method that has been
validated in the literature, which mainly at this point is either blood or skin."

DNA Methylation Versus Telomere Length

One technique used to assess biological aging in the past has been to measure
telomere length. Both Smith and I agree that epigenetic clocks are far superior for this
purpose.

Telomeres are the sequences at the end of your DNA. Every time your cell undergoes a
replication, you lose a little bit of that telomere, making it shorter and shorter over time.
Eventually, you can start losing actual DNA. As the telomere shortens, the cell can start
experiencing problems.

"Telomeres for many years have been thought of as the gold standard for aging
because it's a process which highly correlates to how old someone is because
 they're going to have more replications and more cellular turnover as they get
older," Smith says.

However, in head-to-head comparisons, DNA methylation is significantly more

correlated to the aging process than telomeres. More importantly, it's also more
predictive of health outcomes.

"So, if we're really trying to predict the results, the disease and health span-
related things which are associated with aging, DNA methylation is a much
better way of doing that," Smith says. "That said, telomere length is still one of
those things that is a biomarker of aging. It is a separate process.

If you were to make sure that the telomere length never decreased in a cell,
you'd still see methylation-related biological aging. If you made sure that the
methylation age was reset, you would still see telomere length aging. So, there's
two separate processes.

In a recent review, they actually looked at twins and tried to ascribe how much
of the difference in their aging process was affected by these different markers.
They said right around 2% of the variance in phenotypic aging was due to
telomere length, whereas right around 35% of that was based on these
epigenetic methylation clocks.

So, while they both might be important, we definitely would think that the DNA
methylation clocks are significantly better. But with that being said, we also can
estimate your telomere length via DNA methylation and that's one of the reports
that we do."

DNA Methylation and COVID Outcomes

During the course of the COVID pandemic, Smith has been collaborating with Cornell
University's immunology department, looking at DNA methylation and COVID outcomes.
They were in the fortunate situation of being able to compare pre-COVID measurements
with post-COVID measurements from patients who were getting routinely tested before
the pandemic broke out, and then went on to develop COVID-19.

"We saw some really interesting things as it related to COVID-19 and aging," Smith says.
The first thing they noticed was telomere length shortening. Several studies have now
demonstrated that telomere length decreases with COVID exposure.

"I can't really speculate on the mechanism for that yet, but we definitely know that
several studies with different measurements of telomere length have all concluded the
same thing," Smith says. However, they also found a curious difference in biological
aging as it related to chronological age. He explains:

"In our cohort, which is still relatively small, only 22 people, we saw that people
who were over 50 tended to have advanced ageing as a result of COVID-19
exposure, where they were aging even with mild and moderate disease.
However, people under 50 had a different response. People under 50 actually
showed an anti-aging effect, where they actually got a little bit younger."

The Promise of Very Small Embryonic-Like Stem Cells

Among the more exciting antiaging therapies now available is very small embryonic-like
stem cells (Vsels). Vsels are so small, they're easily transported through the lung
capillary, so if you were to get an IV injection of them, they can spread to the rest of your
body without being broken down or distorted.

Now, your body has mechanisms to replenish Vsels. It's one of the strategies your body
uses to stay healthy. Vsels are extracted from your peripheral blood, unlike regular stem
cells, assuming that they're autologous, which means they're from your own body.
They're not taken from your bone marrow or your fat tissue, which are the two most
common sources for stem cells.

“ With the Vsels and plasma exchange, we are seeing

multiyear age reversals, even with just one or two
 procedures. We're not sure how long that lasts yet ...
but we are seeing — just after the procedure and over a
course of a couple weeks — age reduction in a very
significant way. ~ Ryan Smith
”
Importantly, Vsels are pluripotential, meaning they can differentiate into almost any
tissue in your body, whereas mesenchymal stem cells don't have as much differentiation
capacity. This, I believe, make Vsels an ideal antiaging therapy.

Other Antiaging Strategies Showing Great Promise

Senolytics are also showing promise. A senescent cell is an elderly or aging cell that has
lost the ability to reproduce. It just hangs around, not reproducing and not being cleared
out. As a result, it starts creating inflammatory byproducts.

Senolytics selectively identify these senescent cells and destroy them. That's what
senolytic therapy means. "Seno" meaning it's the senescent cell and "lytic" means that
lyses, i.e., destroys, it.

Another interesting technique is called plasma exchange apheresis. This arose from
studies in which the vascular systems of old and young mice were interconnected so
that the mice started sharing blood with each other. Curiously, the older mice
experienced a rejuvenating effect, and the younger mice experienced more rapid aging.

This led researchers to theorize that there might be something in our blood that
influences aging and phenotypical health process. One evolution of this hypothesis is
taking your own plasma out of your body, filtering it, putting in one or more new
ingredients and then reinfusing it.

Lifestyle Strategies Help Lower Your Biological Age

In closing, here's a list of low-risk strategies that can go a long way toward lowering your
biological age:

• Vitamin D optimization — Ideally, you want to maintain a blood level of 60 ng/mL to

80 ng/mL. Smith cites an interventional trial in which overweight participants
reduced their biological age by 1.8 years on average, taking just 4,000 IUs of oral
vitamin D a day for 16 weeks

• Optimize your metabolic flexibility — Core strategies include time-restricted eating

or intermittent fasting and eating a diet high in healthy fats and low in refined carbs
to optimize your insulin sensitivity, and eating your last meal each day at least three
hours before bed

• Getting regular exercise

• Stress management — According to Smith, people who meditate or engage in other

stress reduction strategies on a regular basis, tend to age at a slower rate than
those who don't

• Limiting consumption of unsaturated fats — Omega-6 linoleic acid (LA) is

particularly harmful. It's highly susceptible to oxidation, causing oxidative stress,
and can remain in your cells for up to a decade. So, you want to eliminate
vegetable/seed oils.

If you're eating a standard American diet, 20% to 25% of your caloric intake can be
LA. I believe this is one of the primary culprits for the massive increase in
degenerative diseases. Before the advent of processed food, the typical intake was
around 2%

More Information

If you're interested in exploring DNA methylation testing for yourself, all of the tests are
available for purchase direct to consumer. The TruAge Complete Collection will give you
the metrics discussed in this interview — everything from telomere length to immune
cell subsets, your intrinsic age, your immune age, and your instantaneous rate of aging.